Overactive bladder(OAB) is a disease that negatively affects the quality of life and occurs symptoms such as increased frequency of urination, urgecy and urinary incontinence. The absence of any local pathological or metabolic cause to clearly explain the symptoms and treatment is aimed at eliminating symptoms with various drugs because of unclear etiology. At this stage, epigenetic factors of the mechanism of overactive bladder have been the subject of research. miRNAs are considered important in regulation of posttranscriptional gene expression of epigenetic factors.
In our study, we aimed to determine the relationship between miRNAs, which may affect the regulation of ADRB3, the adrenergic pathway receptor gene, and ARHGEF10 and ROCK2 the cholinergic receptor pathway, genes, and and overactive bladder. We also investigated whether the detected miRNAs correlated with clinical findings and treatment responses. Additionnaly  we aimed for the effective usability of miRNAs for diagnosis and treatment.

This study was approved by local ethics committee to single-center clinical study. The study included 60 patients with overactive bladder and 60 healthy individuals as a control group. Detailed medical history, physical examinations, necessary laboratory tests and drug use history of all patients were obtained. In this study, patients with neurogenic bladder, bladder outlet obstruction and urinary system diseases or infections such as stones and tumors were applied as exclusion criteria. In healthy volunteers, those with pelvic surgery, any urinary complaints, or drug use were not included in the study. Turkish validated OAB questinnaire form was filled in all patients in the OAB group before and after treatment at the first month. Peripheral venous blood samples were taken from all patient and control groups and RNA isolation was performed according to the relevant commercial kit protocol. After RNA isolation, miRNA expression determination was performed by RT-PCR method. MiRNAs targeting ADRB3, ARHGEF10, ROCK2 gene regions were scanned in targetscan, mirtarbase, microrna.org, dianatools and mirDB databases. Found in four databases and have the highest level of association with these genes that 15 miRNAs were selected. For ADRB3 gene; hsa-let-7a-5p, hsa-let-7c-5p, hsa-let-7e-5p, hsa-let-7f-5p, hsa-let-7g-5p, for ROCK2 gene; için hsa-miR-138-5p, hsa-miR-135b-5p, hsa-miR-300, hsa-miR-381-3p, hsa-miR-200b-3p and for ARHGEF10 gene hsa-miR-520d-3p, hsa-miR-520e, hsa-miR-520a-3p, hsa-miR-373-5p, hsa-miR-372-3p were determined.
The data were analyzed using SPSS 25 version with Mann Whitney U test and MCNemar test for binary categorical comparison.

The patient group was on average 56.48 years old, while the control group was 55.82 years old. In the study, the average height and weight were 156.67 cm and 73.97 kg in the patient group, and 158.78 cm and 72.02 kg in the control group. As a result of the genetic study, the hsa-let-7a-5p (6,8 (0,02 - 97,68)), hsa-let-7c-5p (23,1 (0,31 - 259,57)), hsa-let-7e-5p (7,42 (0,34 - 44,08)), hsa-let-7f-5p (40,93 (0,03 - 484,38)), hsa-let-7g-5p (17,75 (0,44 - 855,13))  genomes associated with ADRB3 in the patient group were high with a high level of significance (p = 0.0001). miR-135b-5p  (0,36 (0,04 - 79,58)), hsa-miR-300 (2,23 (0,14 - 11,63)), hsa-miR-372-3p (5,06 (0,1 - 49,77)), hsa-miR-373-5p (4,54 (0,02 - 61,18)), hsa-miR-381-3p (33,18 (5,16 - 446,39)), hsa-miR-520a-3p (0,7 (0,01 - 9,13)), miR-520d-3p (2,59 (0,03 - 72,86)), hsa-miR-520e (3,27 (0,14 - 19,53)) genomes targeting ARHGEF10 and ROCK2 gene regions were found statistically high in the control group (p = 0.0001). There was no significant difference in hsa-miR-138-5p (p=0,557) and hsa-miR-200b-3p (p=0,157) genomes in the patient and control groups.
At the end of treatment with 1 month anticholinergic agents in the patient group, a significant difference was detected in both miRNAs(hsa-let-7f-5p and miR-135b-5p) in patients with a clinical improvement of 50% and above in the OAB score. hsa-let-7f-5p genome was 147.86 (0.06 - 484.38) in patients with symptom improvement, while it was 32 (0.03 - 426.91) in the group without improvement (p = 0.045). miR-135b-5p genome was found 0.06 (0.03 - 0.21) in patients providing symptom improvement, while it was 0.3 (0.01 - 14.32) in the group without improvement (p = 0.036).

The patient group was on average 56.48 years old, while the control group was 55.82 years old. In the study, the average height and weight were 156.67 cm and 73.97 kg in the patient group, and 158.78 cm and 72.02 kg in the control group. As a result of the genetic study, the hsa-let-7a-5p (6,8 (0,02 - 97,68)), hsa-let-7c-5p (23,1 (0,31 - 259,57)), hsa-let-7e-5p (7,42 (0,34 - 44,08)), hsa-let-7f-5p (40,93 (0,03 - 484,38)), hsa-let-7g-5p (17,75 (0,44 - 855,13))  genomes associated with ADRB3 in the patient group were high with a high level of significance (p = 0.0001). miR-135b-5p  (0,36 (0,04 - 79,58)), hsa-miR-300 (2,23 (0,14 - 11,63)), hsa-miR-372-3p (5,06 (0,1 - 49,77)), hsa-miR-373-5p (4,54 (0,02 - 61,18)), hsa-miR-381-3p (33,18 (5,16 - 446,39)), hsa-miR-520a-3p (0,7 (0,01 - 9,13)), miR-520d-3p (2,59 (0,03 - 72,86)), hsa-miR-520e (3,27 (0,14 - 19,53)) genomes targeting ARHGEF10 and ROCK2 gene regions were found statistically high in the control group (p = 0.0001). There was no significant difference in hsa-miR-138-5p (p=0,557) and hsa-miR-200b-3p (p=0,157) genomes in the patient and control groups.
At the end of treatment with 1 month anticholinergic agents in the patient group, a significant difference was detected in both miRNAs(hsa-let-7f-5p and miR-135b-5p) in patients with a clinical improvement of 50% and above in the OAB score. hsa-let-7f-5p genome was 147.86 (0.06 - 484.38) in patients with symptom improvement, while it was 32 (0.03 - 426.91) in the group without improvement (p = 0.045). miR-135b-5p genome was found 0.06 (0.03 - 0.21) in patients providing symptom improvement, while it was 0.3 (0.01 - 14.32) in the group without improvement (p = 0.036).

OAB is a disease that can significantly reduce the quality of life and the treatment we use today is aimed at reducing the complaints because of the etiopathogenesis of the disease is not fully understood. Today, anticholinergic agents are the most preferred drugs in the medical treatment of OAB. In particular, it appears that anticholinergic drugs do not provide sufficient benefit in some patients. Some patients discontinue treatment due to their side effects. In our study, we determined a significant elevation in miRNAs associated with the adrenergic receptor gene ADRB3 in the patient group. Increased miRNA levels can lead to symptoms of OAB by inhibition of the target gene in several ways. Also, according to our study, miRNA levels effective on the genes in cholinergic pathway were found to be lower than the control group. This may be reducing the inhibition effect on the target gene and in the appearance of AAM symptoms. Better understanding of signaling pathways between the target gene and miRNAs can provide specific treatment strategies, and extensive studies are needed for this area. In the group with a decrease of 50% or more in the OAB score, the hRa-let-7f-5p associated with the ADRB3 receptor gene was higher than the other group and the miR-135b-5p associated with the ROCK2 gene region was lower than the other group. This can also assist the clinician in determining his treatment strategy that who will benefit more. Also, this may prevent patients from unnecessary anticholinergic use and exposure to their side effects, leading to the emergence of more specific treatment strategies and the discovery of new biomarkers that can be used for follow-up treatment. In addition, this study should be supported by more patients and compared with other gene polymorphisms.